title: Multimodal imaging reveals structural and functional heterogeneity in different bone marrow compartments: functional implications on hematopoietic stem cells.
abstract: Intravital microscopy of the calvarium is the only noninvasive method for high-resolution imaging of the bone marrow (BM) and hematopoietic stem cell (HSC) niches. However, it is unclear if the calvarium is representative of all BM compartments. Using the combination of whole body optical imaging, intravital microscopy, and "in vivo fluorescence trapping," a thorough comparison of HSCs and putative HSC niches in the calvaria, epiphyses, and diaphyses, at steady state or after HSC transplantation, can be made. We report substantial heterogeneity between different BM compartments in terms of bone-remodeling activity (BRA), blood volume fraction (BVF), and hypoxia. Although BVF is high in all BM compartments, including areas adjacent to the endosteum, we found that compartments displaying the highest BVF and BRA were preferentially seeded and engrafted upon HSC transplantation. Unexpectedly, the macroanatomical distribution of HSCs at steady state is homogeneous across these 3 areas and independent of these 2 parameters and suggests the existence of "reconstituting niches," which are distinct from "homeostatic niches." Both types of niches were observed in the calvarium, indicating that endochondral ossification, the process needed for the formation of HSC niches during embryogenesis, is dispensable for the formation of HSC niches during adulthood.
authors.affiliation: Haematopoietic Stem Cell Laboratory, Londong Research Institute, Cancer Research UK, London, United Kingdom. francois.lassailly@cancer.org.uk
authors.forename: Francois
authors.initials: F
authors.lastname: Lassailly
authors.forename: Katie
authors.initials: K
authors.lastname: Foster
authors.forename: Lourdes
authors.initials: L
authors.lastname: Lopez-Onieva
authors.forename: Erin
authors.initials: E
authors.lastname: Currie
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000033:anatomy & histology / Q000378:metabolism; D001810:Blood Volume; D001853:Bone Marrow / Q000033:anatomy & histology* / Q000098:blood supply / Q000502:physiology*; D016026:Bone Marrow Transplantation; D016723:Bone Remodeling; D001842:Bone and Bones / Q000098:blood supply / Q000502:physiology; D002451:Cell Compartmentation; D015687:Cell Hypoxia; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006706:Homeostasis; D021621:Imaging, Three-Dimensional / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D010477:Perfusion; D055153:Stem Cell Niche
chemical_list: D015415:Biomarkers